Sequencing platforms (i.e., for example, Illumina GA, ABI SOLiD, Helicoscope) are capable of acquiring vast numbers of sequencing reads and high base coverage at greatly reduced costs. This capacity and cost-effectiveness has opened up new markets and applications for sequencing in the area of functional genomics; that is, the characterization of protein-DNA interactions, chromatin state, copy number variations and RNA expression.
One step in these functional genomic applications is the preparation of DNA libraries suitable for sequencing. Standard library preparation procedures require 0.1-1 μg DNA at the start. This severely limits that applicability of the technologies to experiments in which large amounts of starting sample is available (e.g., millions of cells). As an example, many cell populations and tissues are not amenable to chromatin state analysis due to insufficient cell numbers.
What is needed in the art is a method for preparing DNA sequencing libraries using a source material quantity substantially less than 0.1 μg (i.e., for example, picograms).